4,4,5,5-Tetradehydro-ω-aryl-PGE1 analogs

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which there is a triple bond between C-5 and C-6 or C-4 and C-5. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 619,077, filed Oct. 2, 1975, now issued as U.S. Pat. No. 4,013,695, on Mar. 22, 1977.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,013,695, issued Mar. 22, 1977. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## WHEREIN G IS ONE, 2, OR 3; WHEREIN Y is trans-CH═CH--;wherein M₁ is

    R.sub.5 OH

or

    R.sub.5 OH,

wherein R₅ is hydrogen or methyl; Wherein Z₃ is oxa or methylene, with the proviso that Z₃ is oxa only when R₃ and R₄ are hydrogen or methyl; Wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl; Wherein L₁ is

    R.sub.3 R.sub.4,

    r.sub.3 r.sub.4,

or a mixture of

    R.sub.3 R.sub.4

and

    R.sub.3 R.sub.4,

wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; and Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation.
 2. A compound according to claim 1, wherein M₁ is

    R.sub.5 OH.


3. A compound according to claim 1, wherein M₁ is

    R.sub.5 OH.


4. A compound according to claim 3, wherein g is
 3. 5. A compound according to claim 4, wherein m is
 3. 6. A compound according to claim 5, wherein R₃, R₄, and R₅ are all hydrogen.
 7. 2A, 2B-Dihomo-4,4,5,5-tetradehydro-16-phenoxy-17,18,19,20-tetranor-PGE₁, methyl ester, a compound according to claim
 6. 8. A compound according to claim 3, wherein g is one.
 9. A compound according to claim 8, wherein m is
 3. 10. A compound according to claim 9, wherein R₃ and R₄ are both hydrogen.
 11. A compound according to claim 10, wherein R₅ is methyl.
 12. 4,4,5,5-Tetradehydro-15-methyl-16-phenoxy-17,18,19,20-tetranor-PGE₁, methyl ester, a compound according to claim
 11. 13. 4,4,5,5-Tetrahydro-15-methyl-17-phenyl-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 11. 14. A compound according to claim 10, wherein R₅ is hydrogen.
 15. 4,4,5,5-Tetradehydro-16-phenoxy-17,18,19,20-tetranor-PGE₁, methyl ester, a compound according to claim
 14. 16. 4,4,5,5-Tetradehydro-17-phenyl-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 14. 17. A compound according to claim 9, wherein at least one of R₃ and R₄ is methyl.
 18. A compound according to claim 17, wherein R₃ and R₄ are both methyl.
 19. A compound according to claim 18, wherein R₅ is methyl.
 20. 4,4,5,5-Tetradehydro-15,16-dimethyl-16-phenoxy-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 19. 21. 4,4,5,5-Tetradehydro-15,16,16-trimethyl-17-phenyl-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 19. 22. A compound according to claim 18, wherein R₅ is hydrogen.
 23. 4,4,5,5-Tetradehydro-16-methyl-16-phenoxy-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 22. 24. 4,4,5,5-Tetradehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 22. 25. A compound according to claim 9, wherein at least one of R₃ and R₄ is fluoro.
 26. A compound according to claim 25, wherein R₃ and R₄ are both fluoro.
 27. A compound according to claim 26, wherein R₅ is methyl.
 28. 4,4,5,5-Tetradehydro-15-methyl-16,16-difluoro-17-phenyl-18,19,20-trinor-PGE₁, a compound according to claim
 27. 29. 4,4,5,5-Tetradehydro-15-methyl-16,16-difluoro-17-phenyl-18,19,20-trinor-PGE₁ methyl ester, a compound according to claim
 27. 30. A compound according to claim 26, wherein R₅ is hydrogen.
 31. 4,4,5,5-Tetradehydro-16,16-difluoro-7-phenyl-18,19,20-trinor-PGE₁, a compound according to claim
 30. 32. 4,4,5,5-Tetradehydro-16,17-difluoro-17-phenyl-18,19,20-trinor-PGE₁, methyl ester, a compound according to claim
 30. 